Newswise — New York, NY (May 21, 2020)—Mount Sinai scientists have identified biological markers present in childhood that relate to the degenerative and often fatal neurological disease called amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease, according to a study published in the Annals of Clinical and Translational Neurology in May.
The researchers found the markers in the teeth of patients who went on to develop ALS as adults. They used lasers to map growth rings that form daily in the teeth and discovered evidence in the growth rings formed at birth and within the first 10 years of life that patients with ALS metabolized metals differently than patients without the disease.
ALS is a condition that usually manifests when someone is in their 50s or 60s. The cause is not known, and there is no test to predict its onset. Genetic studies have not revealed a great deal yet, and while experts believe environmental factors play a significant role in the development of the disease, there have been no clear indications of which ones.
“This is the first study to show a clear signature at birth and within the first decade of life, well before any clinical signs or symptoms of the disease,” said senior author Manish Arora, BDS, MPH, PhD, Edith J. Baerwald Professor and Vice Chair of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “We hope in the long term, after validation of this work in larger studies, that this will lead to preventive strategies. What’s exciting about this work is that we are looking at biological pathways that we could potentially modify with drug development.”
The study showed dysregulated uptake of a mixture of essential elements, including zinc and copper, as well as toxins like lead and tin, in 36 ALS patients compared to 31 controls. The markers of metal uptake dysregulation were also observed in teeth from an ALS mouse model that also showed differences in the distribution of metals in the brain compared to controls.
“Our previous work showed that the dysregulation of elemental metabolism in early life was associated with the onset of neurological disease such as autism and ADHD,” said Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, a major contributor to this work. “This study shows that metabolic dysregulation is also associated with neurological conditions with a much greater lag to symptom onset”.
Researchers at the University of Michigan played an important role in this study, and their clinics provided samples and data from ALS patients and patients in the control group.
Dr. Austin and Arora’s work was supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD087523) and the National Institutes of Environmental Health Sciences (DP2ES025453, R01ES024674, U2CES026561,and P30ES023515).
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care—from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.
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Annals of Clinical and Translational Neurology, May 2020